A multiphoton laser microscopy (MPLM) system from Prairie Technologies is requested. The custom system will be assembled in collaboration with the Northwestern University Multiphoton Center Core. The system, developed by Prairie and Northwestern Scientists with software and hardware for simultaneous physiological measurements, consists of two stations: one capable of imaging tissue of live animals, the other for tissue slices. The instrument will be housed in the Research Resources Center (RRC) of the University of Illinois at Chicago. The rapidly expanding Imaging Facility of the RRC provides all research groups at UIC and surrounding institutions access to a full range of EM, optical and image analysis capabilities. The requested MPLM and associated technologies are uniquely suited to imaging of molecules and structures in cells located deep within live tissue sections or living animals. Experiments that require these methodologies cannot be undertaken with the instruments currently at UIC. The intellectual and technological resources necessary to understand complex pathological processes that involve intra and intercellular transport of molecules, development in various model systems, cytoskeletal remodeling, axonal transport, immunology, viral entry, tumor formation, signaling and molecular imaging are in place. The MPLM technology will be critical in advancing our research programs as well as fostering interactions among investigators with diverse but compatible interests. Our overall objective as a group is to understand the dynamic molecular events that occur within the context of specific tissues. This is particularly critical in complex tissues like the nervous system, developing embryos, endocrine organs, where relationships between different cell types cannot be replicated in isolated cultures. MPLM imaging will provide us with heretofore unavailable windows on basic molecular interactions among key proteins involved in intracellular trafficking, cell signaling, and pathogenesis. Our strengths, as an interdisciplinary research group with basic and applied research programs in Development, Cell Physiology, Neuroscience, Virology and Immunology, provide the basis of the need for this instrumentation. The addition of the proposed MPLM system will provide a unique capability relevant to several key NIH funded investigators where we have a nationally-recognized track-record in axonal transport and neurodegeneration, virus entry and trafficking, cytoskeletal protein remodeling, cancer, immunology, signal transduction, and molecular imaging. We believe that the insights gained will have the potential for pioneering new therapeutic targets and strategies in HIV prevention, cancer, autoimmune disease, diabetes, and neurodegeneration.